title: An envirogenomic signature is associated with risk of IBD-related surgery in a population-based Crohn's disease cohort.
abstract: OBJECTIVE
  Crohn's disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach.
  
  
  METHODS
  We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable.
  
  
  RESULTS
  A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95% CI P = 1 × 10(-4)) which was higher than any factor considered independently.
  
  
  CONCLUSIONS
  The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.
authors.affiliation: Genomics Research Centre, Griffith Health Institute, School of Medical Sciences, Griffith University, Gold Coast Campus, Southport, 4222, QLD, Australia.
authors.forename: Bushra F
authors.initials: BF
authors.lastname: Nasir
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
authors.forename: Aslam
authors.initials: A
authors.lastname: Nasir
authors.forename: Rebecca
authors.initials: R
authors.lastname: Roberts
authors.forename: Murray
authors.initials: M
authors.lastname: Barclay
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gearry
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Lea
mesh_terms: D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D015331:Cohort Studies; D003424:Crohn Disease / Q000209:etiology / Q000601:surgery*; D003661:Decision Support Techniques; D004032:Diet; D004777:Environment; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008019:Life Style; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D005819:Genetic Markers; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein